Recombinant tumor necrosis factor (rTNF) inhibits erythropoiesis. We added rTNF to human CFU-E and found marked inhibition, which disappeared after purification of the CFU-E. Inhibition of colony growth was restored by adding back accessory cells or conditioned medium from cells stimulated by rTNF. These studies indicate that the anemia of chronic disease is not a direct effect of TNF but an indirect effect.